Ms. R, age 44, is referred by her primary care physician. She complains of tenseness, irritability, avolition, and fatigue. She worries incessantly that her children will get sick, a catastrophe will befall her husband, or she’ll do something wrong. She says she sometimes feels as if she’s thinking “a zillion racing thoughts.”

Once fun-loving, outgoing, and energetic, Ms. R says she began feeling unusually anxious 3 years ago. A psychiatrist diagnosed bipolar disorder type II based on her racing thoughts, irritability, low energy, and history of mood swings. Over 2 years, the psychiatrist tried combining valproic acid with bupropion, citalopram, or extended-release venlafaxine, then tried lithium monotherapy. Nothing worked.

Frustrated, Ms. R left the psychiatrist and consulted her primary care physician, who prescribed gabapentin, 200 mg each morning and 300 mg at night; fluoxetine, 50 mg/d; and quetiapine, 12.5 mg/d. Ms. R noticed no improvement and stopped the medications after 6 weeks. The physician urged her to see another psychiatrist, and she presented to us 2 weeks after stopping the medications.

Ms. R also has been feeling depressed and irritable the past 4 months and has trouble falling and staying asleep at night. She sleeps 4 to 5 hours nightly, constantly feels tired, cannot concentrate, and overeats to try to alleviate her stress. She has gained 6 pounds over 2 to 3 months and weighs 160 lb; her body mass index of 26 indicates she is overweight.

She says her worries overwhelm her and cause heart palpitations and muscle tension in her neck and shoulders. She admits to feeling “worthless,” but denies suicidal thoughts.

Ms. R describes her husband and two teenage daughters as “very supportive,” but admits that her fatigue and irritability have strained these relationships; she says she snaps at them for minor things, such as coming to dinner 1 minute late. She misses her job, which she recently quit because of her decreasing ability to function.

At intake, Ms. R says she will not resume previous medications but will consider alternatives. She refuses psychotherapy because of time constraints and transportation problems but is willing to return every 2 weeks for medication checks. She says she adhered to every prescription over 3 years with no major side effects. She has never taken an antidepressant or anxiolytic without a mood stabilizer.

Ms. R reports no medical problems, past substance use, current or past psychotic symptoms, or psychiatric hospitalizations. Her family history shows depression in one first-degree relative and anxiety in others. Her Hamilton Anxiety Scale (HAM-A) score of 20 indicates moderate anxiety. Laboratory tests ordered by her primary care physician are normal.

Does Ms. R have depression? Determining if the patient’s depressive symptoms are secondary to GAD or warrant a separate diagnosis can be difficult (Table 1). With Ms. R’s permission, we talked to her family, because collateral information often helps clarify the diagnosis. Her husband and daughters offered no significant new insights, however.

Table 1

Overlap among symptoms that suggest GAD, mania, or major depression

Symptom

GAD

Mania

MDD

Difficulty concentrating/distractibility

X

X

X

Mood irritability

X

X

X

‘Racing’ thoughts

X

X

X

Sleep disturbance

X

X

X

Tiring easily/low energy

X

X

Ecessive psychomotor activity/restlessness

X

X

X

GAD: generalized anxiety disorder

MDD: major depressive disorder

Source: Reference 1

Treatment: Targeting the anxiety

To address Ms. R’s anxiety symptoms, we start buspirone, 5 mg tid, and titrate to 15 mg bid over 2 weeks. We choose buspirone—which is FDA-approved to treat GAD—because it is unlikely to cause a mood switch if bipolar disorder is causing Ms. R’s depression. We discuss with her the drug’s indications, benefits, and potential side effects (such as vertigo, headache, lightheadedness, and nausea).

At the first 2-week follow-up, Ms. R reports no side effects but little improvement. After another 2 weeks, she says she feels less anxiety, irritability, pain, and fewer racing thoughts. She reports less difficulty falling asleep, though she’s still sleeping only about 6 hours nightly. Her HAM-A score falls to 12, indicating mild anxiety.